Mycotoxins are some of the most prevalent toxins in the
environment. These molecules are secondary metabolites of fungi. (1)
Most humans are exposed to mycotoxins through mold, which can be found
growing in buildings, vehicles, and foodstuffs. Mold can grow on almost
any surface, especially if the environment is warm and wet. Inner wall
materials of buildings, wall paper, fiber glass insulation, ceiling
tiles, and gypsum support are all good surfaces for mold to colonize.
The mold can then release mycotoxins into the environment causing
symptoms of many different chronic diseases. Diseases and symptoms
linked to mycotoxin exposure include immune-suppression, fever,
pneumonia-like symptoms, heart disease, rheumatic disease, asthma,
sinusitis, cancer, memory loss, vision loss, chronic fatigue, skin
rashes, depression, ADHD, anxiety, and liver damage. (2,3)

Mycotoxins are absorbed in the mucosal epithelia in the airways and
the gut and can affect many immune-related organs and cell types. (4)
These interactions suppress immune functions. Multiple types of
mycotoxins can cause a decrease in B cells, white blood cells, and
hematopoietic stem cells. (5,6) Exposure to mycotoxins decreases the
amount of mature CD4+ cells and splenic T lymphocytes. (7) This exposure
will also affect different groups of cytokines. IL-2 production and IL-2
receptors are decreased, but IL-17, IL-10, TGF-[alpha], and MIP-1[beta]
are all elevated. These changes in cytokine expression can lead to
enhanced tissue damage to multiple different tissues and organs. (8)

Mycotoxins and the Brain

One of the main organs affected by mycotoxins is the brain. (9)
Mycotoxin inhibition of protein synthesis, damage to DNA, and increased
production of inflammatory cytokines lead to damage of the central
nervous system (CNS). (10) Mycotoxins also affect the proliferation and
migration of neurons. (11) Neurotoxicity is most pronounced in the
ventral mesencephalon, hippocampus, and striatum. (12) The blood brain
barrier, which is a selective permeable barrier protecting the brain,
can be damaged by mycotoxins. Trichothecenes can cause cytotoxic effects
at the blood brain barrier, which will allow other harmful chemicals and
pathogens to affect the brain. (13) In the brain, proinflammatory
cytokine interleukin 1[beta] is produced during mycotoxin exposure. (14)
Damage caused by mycotoxin exposure can lead to depression, poor memory
recall, Alzheimer's-like symptoms, and headaches. (15)

Introducing the GPL-MycoTOX Profile

At The Great Plains Laboratory, Inc., we have a primary focus on
helping patients with chronic illnesses, including mental health
disorders. We have developed tests that look at hundreds of different
analytes and have worked with doctors to help them interpret how these
data can be used to personalize treatment for patients. Our newest test,
the GPL-MycoTOX Profile (a urine test), was developed to combat the
pervasive problem of mold exposure. We have heard from our clients that
the marketplace lacked an accurate and affordable test to measure
mycotoxins. We decided to use our expertise in liquid chromatography
mass spectrometry (LC/MS) to meet this need. Using this technology, we
have a very sensitive test, which is important because mycotoxins can
cause serious health issues even in small quantities. Other mycotoxin
testing uses ELISA technology, which relies on antibodies. Utilization
of LC-MS/MS technology gives us a precise identification of all of our
analytes, which prevents having false positive errors. For many of our
compounds we are able to detect amounts in the parts per trillion (ppt),
which is about 100-fold better than any other test currently available.

Species of Mold

We are currently measuring seven different markers in our test from
multiple species of mold. This makes the GPL-MycoTOX Profile the most
comprehensive mycotoxin test on the market. It is also the most
cost-effective. Here are four of the genuses of mold we are evaluating:
Aspergillus, Penicillium, Stachybotrys, and Fusarium.

Aspergillus is the most prevalent mold group in the environment. It
has caused billions of dollars in damage to crops and livestock. The
most common Aspergillus mycotoxins are aflatoxin, ochratoxin, patulin,
and fumagillin. The main target of these toxins is the liver. These
toxins have been found in all major cereal crops including peanuts,
corn, cotton, millet, rice, sorghum, sunflower seeds, wheat, and a
variety of spices. They are also found in eggs, milk, and meat from
animals fed contaminated grains. Diseases caused by Aspergillus are
called aspergillosis. The most common route of infection is through the
respiratory system. Aspergillus can cause severe asthma when the mold
colonizes the lung, forming a granulomatous disease. (16)

There are over 200 species of Penicillium that have been
discovered. It is often found in indoor environments and is responsible
for many allergic reactions. Penicillium is also a known contaminate in
many different food items. Several different types of citrus fruits can
become contaminated with Penicillium, but it can also contaminate seeds
and grains. One reason that Penicillium is so common is because of its
ability to thrive in low humidity. In the home, Penicillium can be found
in wallpaper, carpet, furniture, and fiberglass insulation. The most
common mycotoxin produced by Penicillium is ochratoxin. Ochratoxin is
nephrotoxic, which means that it damages the kidneys. It is also
carcinogenic. (17)

Stachybotrys is a greenish-black mold. This mold can grow on
materials with high cellulose and low nitrogen content such as gypsum
board, paper, fiberboard, and ceiling tiles. Stachybotrys is known for
its production of the highly toxic macrocyclic trichothecene mycotoxins,
which can be extremely neurotoxic. Two of the more common mycotoxins
produced by Stachybotrys are roridin E and verrucarin. In addition to
these mycotoxins, the fungus produces nine phenylspirodrimanes, as well
as cyclosporine, which are potent immunosuppressors. These
immunosuppressors, along with the mycotoxin trichothecenes, may be
responsible for the high toxicity of Stachybotrys. (16)

Fusarium's major mycotoxins are zearalenone (ZEN) and
fumonisin. Fusarium fungi grow best in temperate climate conditions.
They require lower temperatures for growth than Aspergillus. Fusarium
grows worldwide on many different types of grains including corn and
wheat. Exposure to mycotoxins from Fusarium can lead to both acute and
chronic effects. These symptoms can include abdominal distress, malaise,
diarrhea, emesis, and death. ZEN possesses estrogenic effects and has
been implicated in reproductive disorders. (18)

Markers in the GPL-MycoTOX Profile

The seven different markers for mycotoxins in our GPL-MycoTOX
Profile provide extensive coverage, allowing us to catch most mold
exposures.

Aflatoxin M1: Aflatoxin Ml (AFM1) is the main metabolite of
aflatoxin Bl, which is a mycotoxin produced by the mold genus
Aspergillus. Aflatoxins are some of the most carcinogenic substances in
the environment. Aflatoxin susceptibility is dependent on multiple
different factors such as age, sex, and diet. Aflatoxin can be found in
beans, corn, rice, tree nuts, wheat, milk, eggs, and meat. In cases of
lung aspergilloma, aflatoxin has been found in human tissue specimens.
Aflatoxin can cause liver damage, cancer, mental impairment, abdominal
pain, hemorrhaging, coma, and death. Aflatoxin has been shown to inhibit
leucocyte proliferation. Clinical signs of aflatoxicosis are
non-pruritic macular rash, headache, gastrointestinal dysfunction (often
extreme), lower extremity edema, anemia, and jaundice. The toxicity of
aflatoxin is increased in the presence of ochratoxin and zearalenone.
(19)

Ochratoxin: Ochratoxin A (OTA) is a nephrotoxic, immunotoxic, and
carcinogenic mycotoxin. This chemical is produced by molds in the
Aspergillus and Penicillium genuses. Exposure is primarily through
contaminated foods such as cereals, grape juices, dairy, spices, wine,
dried vine fruit, and coffee. Exposure to OTA can also come from
inhalation exposure in water-damaged buildings. OTA can lead to kidney
disease and adverse neurological effects. Studies have shown that OTA
can cause significant oxidative damage to multiple brain regions and the
kidneys. Dopamine levels in the brain of mice have been shown to be
decreased after exposure to OTA. (20)

Sterigmatocystin (STC): STC is a mycotoxin that is closely related
to aflatoxin. STC is produced from several genuses of mold such as
Aspergillus, Penicillium, and Bipolaris. It is considered to be
carcinogenic, particularly in the cells of the Gl tract and liver. STC
has been found in the dust from damp carpets. It is also a contaminant
of many foods including grains, corn, bread, cheese, spices, coffee
beans, soybeans, pistachio nuts, and animal feed. In cases of lung
aspergilloma, STC has been found in human tissue specimens. The toxicity
of STC affects the liver, kidneys, and immune system. Tumors have been
found in the lungs of rodents that were exposed to STC. Oxidative stress
becomes measurably elevated during STC exposure, which causes a
depletion of antioxidants such as glutathione, particularly in the
liver. (21)

Zearalenone (ZEN): ZEN is a mycotoxin that is produced by the mold
Fusarium, and has been shown to be hepatotoxic, haematotoxic,
immunotoxic, and genotoxic. ZEN is commonly found in several foods in
the US, Europe, Asia, and Africa including wheat, barley, rice, and
maize. ZEN has estrogenic activity and exposure to ZEN can lead to
reproductive changes. ZEN's estrogenic activity is higher than that
of other non-steroidal isoflavones (compounds that have estrogen-like
effects) such as soy and clover. ZEN exposure can result in thymus
atrophy and alter spleen lymphocyte production as well as impair
lymphocyte immune response, which leads to patients being susceptible to
disease. (22)

Roridin E and Verrucarin A: Roridin E and verrucarin A are
macrocyclic trichothecenes produced by the mold genuses Fusarium,
Myrothecium, and Stachybotrys (i.e. black mold). Trichothecenes are
frequently found in buildings with water damage but can also be found in
contaminated grain. These are very toxic compounds, which inhibit
protein biosynthesis by preventing peptidyl transferase activity.
Trichothecenes are considered extremely toxic and have been used as
biological warfare agents. Even low levels of exposure to macrocyclic
trichothecenes can cause severe neurological damage, immunosuppression,
endocrine disruption, cardiovascular problems, and gastrointestinal
distress. (23)

Enniatin B: This is a fungal metabolite categorized as a cyclohexa
depsipeptides toxin produced by the fungus Fusarium. This fungus is one
of the most common cereal contaminants. Grains in many different
countries have recently been contaminated with high levels of enniatin.
The toxic effects of enniatin are caused by the inhibition of the
acyl-CoA cholesterol acyltransferase, depolarization of mitochondria,
and inhibition of osteoclastic bone resorption. Enniatin has antibiotic
properties, and chronic exposure may lead to weight loss, fatigue, and
liver disease. (24)

Summary

Mycotoxins from mold are some of the most common and toxic
compounds we are exposed to, and they can be incredibly harmful to our
mental and physical health. The neurotoxicity caused by mycotoxins can
lead to a variety of neurological and neuropsychiatric problems
including depression, memory loss, and Alzheimer's-like symptoms.
Mycotoxins also cause many other health problems and can be
carcinogenic. The Great Plains Laboratory, Inc. offers cuttingedge
diagnostic tools that help identify underlying causes of symptoms like
these and provides recommendations for treatment based on test results.
The new GPL-MycoTOX Profile is a highly accurate and affordable urine
test for mycotoxin exposure that can be run with our other urine tests
including the Organic Acids Test (OAT), GPL-TOX (Toxic Non-Metal
Chemical Profile), and the Phospholipase A2 Activity Test (PLA2). All of
these tests are incredibly clinically useful in the assessment of
underlying contributors to mental health and neurological disorders.
Utilizing this combination of tests will help practitioners discover the
underlying causes of many of their patient's symptoms, whether
neurological, psychiatric, or otherwise.

Matthew Pratt-Hyatt, Associate Director of The Great Plains
Laboratory, Inc., received his PhD in cellular and molecular biology
from the University of Michigan. At The Great Plains Laboratory, he is
focused on assisting with diagnosis and treatment of mitochondrial
disorders, neurological diseases, chronic immune diseases, and more. He
specializes in developing tools that examine factors at the interface
between genetics and toxicology. His work is bringing new insight into
how genes and toxicants interact and how that interaction may lead to
mental health disorders, chronic health issues, and metabolism
disorders.

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